Liver disease has emerged as one of the leading causes of morbidity and mortality of HIV-infected individuals in the HAART era, which is primarily due to chronic hepatitis B and C infections. Recreational drug use has also increased over the past few years, and it can affect the liver as well. It has been challenging to evaluate and understand liver disease in HIV-infected persons due to the lack of non-invasive methods to evaluate liver disease. Recently, Dr. Mehta and colleagues demonstrated that glycosylation of immunoglobulin G reactive to the heterophilic alpha-gal epitope increases with advancing liver disease. This glycosylation leads to increased binding to a fucose binding lectin, Aleuria aurantia (AAL). The hypothesis of this proposal is that viral hepatitis liver- related disease is improved with HAART and is affected by drug use. In this proposal, AAL reactivity will be used as a marker of liver disease. This hypothesis will be tested through the following two Aims using participants from the Multicenter AIDS Cohort Study (MACS). The first Aim is a cross-sectional and will utilize samples prior to initiation of HAART. This Aim is designed to determine if AAL reactivity is higher in persons co- infected with HIV and hepatitis B or C compared to persons with either HIV or viral hepatitis alone, or none of these infections. AAL reactivity is expected to be higher in the co-infected group since HIV is known to exacerbate liver disease progression. The second Aim is prospective and will follow AAL reactivity in the individuals in Aim 1 at 3 and 6 years after the sample tested in Aim 1. The change in AAL reactivity over time will be determined in each individual and compared based on the HIV/hepatitis and HAART status. In addition, the effect of drug use and other covariates on AAL reactivity will be modeled. If control of HIV with HAART improves hepatitis-related liver disease, we would expect that the co-infected subjects on HAART would have decreased AAL reactivity over time. This improvement could be modified by drug use since recreational drugs can be hepatotoxic. Understanding liver disease and the effects of recreational drug use in the HAART era is important for determining optimal treatment of HIV-viral hepatitis co-infected individuals. Liver disease has emerged as one of the leading causes of morbidity and mortality of HIV-infected individuals during the HAART era and is primarily from chronic hepatitis B and C infections. The chief purpose of this investigation is use a novel serum marker (glycosylation of a particular IgG molecule) to determine change in liver disease stage prospectively with HAART in HIV-viral hepatitis co-infected MACS participants. Such information will help to optimize treatment of HIV-viral hepatitis co-infected individuals.